title: Clinical-pathologic significance of cancer stem cell marker expression in familial breast cancers.
abstract: Human breast cancer cells with a CD44(+)/CD24(-/low) or ALDH1+ phenotype have been demonstrated to be enriched for cancer stem cells (CSCs) using in vitro and in vivo techniques. The aim of this study was to determine the association between CD44(+)/CD24(-/low) and ALDH1 expression with clinical-pathologic tumor characteristics, tumor molecular subtype, and survival in a well characterized collection of familial breast cancer cases. 364 familial breast cancers from the Ontario Familial Breast Cancer Registry (58 BRCA1-associated, 64 BRCA2-associated, and 242 familial non-BRCA1/2 cancers) were studied. Each tumor had a centralized pathology review performed. TMA sections of all tumors were analyzed for the expression of ER, PR, HER2, CK5, CK14, EGFR, CD44, CD24, and ALDH1. The Chi square test or Fisher's exact test was used to analyze the marker associations with clinical-pathologic tumor variables, molecular subtype and genetic subtype. Analyses of the association of overall survival (OS) with marker status were conducted using Kaplan-Meier plots and log-rank tests. The CD44(+)/CD24(-/low) and ALDH1+ phenotypes were identified in 16% and 15% of the familial breast cancer cases, respectively, and associated with high-tumor grade, a high-mitotic count, and component features of the medullary type of breast cancer. CD44(+)/CD24(-/low) and ALDH1 expression in this series were further associated with the basal-like molecular subtype and the CD44(+)/CD24(-/low) phenotype was independently associated with BRCA1 mutational status. The currently accepted breast CSCs markers are present in a minority of familial breast cancers. Whereas the presence of these markers is correlated with several poor prognostic features and the basal-like subtype of breast cancer, they do not predict OS.
authors.affiliation: Department of Pathology and Molecular Medicine, Juravinski Hospital and Cancer Centre, McMaster University, 711 Concession St., Hamilton, ON, Canada. bane@hhsc.ca
authors.forename: Anita
authors.initials: A
authors.lastname: Bane
authors.forename: Alicia
authors.initials: A
authors.lastname: Viloria-Petit
authors.forename: Dushanthi
authors.initials: D
authors.lastname: Pinnaduwage
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Mulligan
authors.forename: Frances P
authors.initials: FP
authors.lastname: O'Malley
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
mesh_terms: D000328:Adult; D000080924:Aldehyde Dehydrogenase 1 Family; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000151:congenital* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009864:Ontario; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase